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Transplant immunology

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https://www.readbyqxmd.com/read/28340245/unacceptable-human-leucocyte-antigens-for-organ-offers-in-the-era-of-organ-shortage-influence-on-waiting-time-before-kidney-transplantation
#1
Malte Ziemann, Nicole Heßler, Inke R König, Nils Lachmann, Andrea Dick, Vanessa Ditt, Klemens Budde, Petra Reinke, Ute Eisenberger, Barbara Suwelack, Thomas Klein, Timm H Westhoff, Wolfgang Arns, Katrin Ivens, Antje Habicht, Lutz Renders, Dirk Stippel, Dominik Bös, Florian Sommer, Siegfried Görg, Martin Nitschke, Thorsten Feldkamp, Falko M Heinemann, Reinhard Kelsch
Background.: The assignment of human leucocyte antigens (HLAs) against which antibodies are detected as unacceptable antigens (UAGs) avoids allocation of HLA- incompatible allografts. There is uncertainty as to what extent UAGs decrease the probability of receiving a kidney offer. Methods.: Kidney transplantations in 3264 patients on the waiting lists of six German transplant centres were evaluated for a period of at least 2 years. The proportion of excluded offers due to UAGs was calculated as virtual panel-reactive antibodies (vPRAs)...
March 15, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28338506/a-preliminary-report-radical-surgery-and-stem-cell-transplantation-for-the-treatment-of-patients-with-pancreatic-cancer
#2
Brigitta Omazic, Burcu Ayoglu, Matthias Löhr, Ralf Segersvärd, Caroline Verbeke, Isabelle Magalhaes, Zuzana Potacova, Jonas Mattsson, Alexei Terman, Sam Ghazi, Nils Albiin, Nikolaos Kartalis, Peter Nilsson, Thomas Poiret, Liu Zhenjiang, Rainer Heuchel, Jochen M Schwenk, Johan Permert, Markus J Maeurer, Olle Ringden
We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of pancreatic ductal adenocarcinoma, a deadly disease with a median survival of 24 months for resected tumors and a 5-year survival rate of 6%. After adjuvant chemotherapy, 2 patients with resected pancreatic ductal adenocarcinoma underwent HSCT with HLA-identical sibling donors. Comparable patients who underwent radical surgery, but did not have a donor, served as controls (n=6). Both patients developed humoral and cellular (ie, HLA-A*01:01-restricted) immune responses directed against 2 novel tumor-associated antigens (TAAs), INO80E and UCLH3 after HSCT...
March 23, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28332287/pretransplant-numbers-of-cd16-monocytes-as-a-novel-biomarker-to-predict-acute-rejection-after-kidney-transplantation-a-pilot-study
#3
Thierry P P van den Bosch, Luuk B Hilbrands, Rens Kraaijeveld, Nicolle H R Litjens, Farhad Rezaee, Daan Nieboer, Ewout W Steyerberg, Judith A van Gestel, Dave L Roelen, Marian C Clahsen-van Groningen, Carla C Baan, Ajda T Rowshani
Acute rejection is one of the major immunological determinants of kidney graft function and survival. Early biomarkers to predict rejection are lacking. Emerging evidence reveals a crucial role for the monocyte-macrophage lineage cells in the pathogenesis of rejection. We hypothesized that higher pre-transplant numbers of proinflammatory CD16+ monocytes can predict rejection. The study cohort consisted of 104 kidney transplant recipients (58 no-rejections and 46 biopsy-proven rejections), and 33 healthy individuals...
March 23, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28328655/vascularized-composite-allotransplantation-an-emerging-concept-for-burn-reconstruction
#4
Zhi Yang Ng, Alexandre G Lellouch, Tessa Drijkoningen, Irene A Chang, David H Sachs, Curtis L Cetrulo
Vascularized composite allotransplantation (VCA) has demonstrated utility in the reconstruction of extensive soft-tissue defects following severe burns. However, pre-VCA events such as multiple transfusions, previous transplantation and pregnancies, the use of skin allografts, and mechanical support devices may result in sensitization and ultimately exclude a burn patient, who may benefit most through VCA, from a hand or face transplant. The authors sought to identify the immunologic challenges involved. All reported VCA cases up to July 2016 were reviewed...
March 15, 2017: Journal of Burn Care & Research: Official Publication of the American Burn Association
https://www.readbyqxmd.com/read/28321910/the-coming-of-age-of-a-young-subspecialty-paediatric-hepatology
#5
REVIEW
Antal Németh
Paediatric hepatology dates from the 1970s and it is the youngest of the organ-specific subspecialties. Since then there have been impressive achievements in the fields of anatomical, metabolic, immunological and neoplastic diseases and the advent of modern molecular biology has resulted in a marked increase in exact diagnoses. Liver transplants provided enormous stimulus for the discipline. Due to changing morbidity patterns the discipline faces new challenges, such as environmental and lifestyle induced liver diseases, but different forms of chronic viral hepatitis are diminishing...
March 21, 2017: Acta Paediatrica
https://www.readbyqxmd.com/read/28321224/specific-igg-antibodies-react-to-mimotopes-of-bk-polyomavirus-a-small-dna-tumor-virus-in-healthy-adult-sera
#6
Silvia Pietrobon, Ilaria Bononi, Elisa Mazzoni, Francesca Lotito, Marco Manfrini, Andrea Puozzo, Federica Destro, Giovanni Guerra, Pier Francesco Nocini, Fernanda Martini, Mauro G Tognon
BK polyomavirus (BKPyV) was isolated in 1971 from the urine of a kidney transplant patient. Soon after its identification, BKPyV was characterized as a kidney-tropic virus, which is responsible of a significant fraction of the rejection of transplant kidney in the host. Moreover, in experimental conditions, BKPyV is able to transform different types of animal and human cells and to induce tumors of different histotypes in experimental animals. BKPyV DNA sequences have been detected in healthy individuals and cancer patients using polymerase chain reaction/Shouthern blot hybridization methods...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28320631/outcomes-of-adolescent-recipients-after-lung-transplantation-an-analysis-of-the-international-society-for-heart-and-lung-transplantation-registry
#7
Miranda A Paraskeva, Leah B Edwards, Bronwyn Levvey, Josef Stehlik, Samuel Goldfarb, Roger D Yusen, Glen P Westall, Greg I Snell
BACKGROUND: Recipient adolescent age for non-lung solid-organ transplantation is associated with higher rates of rejection, graft loss and mortality. Although there have been no studies specifically examining adolescent outcomes after lung transplantation (LTx), limited data from the International Society of Heart and Lung Transplantation (ISHLT) Registry suggest that a similar association may exist. Recently, adolescence has been defined as 10 to 24 years of age, taking into account the biologic and sociologic transitions that occur during this age interval...
February 17, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28320105/anti-fibrotic-potential-of-human-umbilical-cord-mononuclear-cells-and-mouse-bone-marrow-cells-in-ccl4-induced-liver-fibrosis-in-mice
#8
Nageh Ahmed Elmahdy, Samia Salem Sokar, Mohamed Labib Salem, Naglaa Ibrahim Sarhan, Sherin Hamed Abou-Elela
Liver fibrosis is the consequence of hepatocyte injury that leads to the activation of hepatic stellate cells (HSC). The treatment of choice is Liver transplantation; however, it has many problems such as surgery-related complications, immunological rejection and high costs associated with the procedure. Stem cell-based therapy would be a potential alternative, so the aim of this study is to investigate the therapeutic potential of human umbilical cord mononuclear cells (MNC) and mouse bone marrow cells (BMC) against carbon tetrachloride (CCl4) induced liver fibrosis in mice and compare it with that of silymarin...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28319446/good-laboratory-practice-preclinical-safety-studies-for-gsk2696273-mlv-vector-based-ex-vivo-gene-therapy-for-adenosine-deaminase-deficiency-severe-combined-immunodeficiency-in-nsg-mice
#9
Nicola Carriglio, Jan Klapwijk, Raisa Jofra Hernandez, Michela Vezzoli, Franck Chanut, Rhiannon Lowe, Draghici Elena, Melanie Nord, Paola Albertini, Patrizia Cristofori, Jane Richards, Hazel Staton, Jonathan Appleby, Alessandro Aiuti, Aisha V Sauer
GSK2696273 (autologous CD34+ cells transduced with retroviral vector that encodes for the human adenosine deaminase [ADA] enzyme) is a gamma-retroviral ex vivo gene therapy of bone marrow-derived CD34+ cells for the treatment of adenosine deaminase deficiency severe combined immunodeficiency (ADA-SCID). ADA-SCID is a severe monogenic disease characterized by immunologic and nonimmunologic symptoms. Bone-marrow transplant from a matched related donor is the treatment of choice, but it is available for only a small proportion of patients...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28319074/tregs-hype-or-hope-for-allogeneic-hematopoietic-stem-cell-transplantation
#10
REVIEW
F Lussana, M Di Ianni, A Rambaldi
The discovery of T regulatory cells has been one of the most important advances in basic immunology and has opened the door to the development of innovative therapeutic strategies for improving the outcome of solid organ and hematopoietic stem cell transplantation. Basic immunology is rapidly elucidating the complex biology of these cells even though the difficulties in purifying or even expanding them in vitro represent a major limitation to the development of clinical studies. The clinical benefit potentially associated with this therapeutic approach remains to be demonstrated...
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28319051/tissue-specific-exosome-biomarkers-for-noninvasively-monitoring-immunologic-rejection-of-transplanted-tissue
#11
Prashanth Vallabhajosyula, Laxminarayana Korutla, Andreas Habertheuer, Ming Yu, Susan Rostami, Chao-Xing Yuan, Sanjana Reddy, Chengyang Liu, Varun Korutla, Brigitte Koeberlein, Jennifer Trofe-Clark, Michael R Rickels, Ali Naji
In transplantation, there is a critical need for noninvasive biomarker platforms for monitoring immunologic rejection. We hypothesized that transplanted tissues release donor-specific exosomes into recipient circulation and that the quantitation and profiling of donor intra-exosomal cargoes may constitute a biomarker platform for monitoring rejection. Here, we have tested this hypothesis in a human-into-mouse xenogeneic islet transplant model and validated the concept in clinical settings of islet and renal transplantation...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28316190/-allogeneic-cultured-limbal-epithelial-transplantation-a-clinical-observation-of-its-treatment-effects-on-large-conjunctival-lesions
#12
J Cheng, J Y Wang, H Y Duan, S Wang, L Cong, L X Xie
Objective: To introduce the surgical methods and investigate the treatment effects of conjunctival lesion resection combined with transplantation of allogeneic limbal epithelia cultured in vitro for treatment of varied large conjunctival lesions. Methods: A retrospective analysis of case data of the patients receiving transplantation of allogeneic limbal epithelia cultured in vitro for large conjunctival lesions at Qingdao Eye Hospital from January 2013 to December 2015 was conducted. Fresh donor corneal limbal epithelial tissues were obtained for cellular digestion and isolation...
March 11, 2017: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
https://www.readbyqxmd.com/read/28314211/the-role-of-kupffer-cells-in-hepatic-diseases
#13
REVIEW
Peizhi Li, Kun He, Jinzheng Li, Zuojin Liu, Jianping Gong
Kupffer cells (KCs) constitute 80-90% of the tissue macrophages present in the body. Essential to innate and adaptive immunity, KCs are responsible for the swift containment and clearance of exogenous particulates and immunoreactive materials which are perceived as foreign and harmful to the body. Similar to other macrophages, KCs also sense endogenous molecular signals that may result from perturbed homeostasis of the host. KCs have been implicated in host defense and the pathogenesis of various hepatic diseases, including endotoxin tolerance, liver transplantation, nonalcoholic fatty liver disease, and alcoholic liver disease...
March 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28306593/current-concepts-for-sensitized-patients-before-transplantation
#14
Dael Geft, Jon Kobashigawa
PURPOSE OF REVIEW: Antibody allosensitization poses a major immunologic challenge for patients awaiting heart transplantation. It is associated with significant morbidity and mortality for both pretransplant and posttransplant patients by prolonging wait times to transplant and increasing posttransplant rejection and vasculopathy. Many questions remain regarding methods and interpretation of antibody detection, the relevance of sensitization in specific patient populations such as those with mechanical circulatory support and the ideal strategies for desensitization...
March 16, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28303661/immunological-and-physiological-observations-in-baboons-with-life-supporting-genetically-engineered-pig-kidney-grafts
#15
Hayato Iwase, Hidetaka Hara, Mohamed Ezzelarab, Tao Li, Zhongqiang Zhang, Bingsi Gao, Hong Liu, Cassandra Long, Yi Wang, Amy Cassano, Edwin Klein, Carol Phelps, David Ayares, Abhinav Humar, Martin Wijkstrom, David K C Cooper
BACKGROUND: Genetically engineered pigs could provide a source of kidneys for clinical transplantation. The two longest kidney graft survivals reported to date have been 136 and 310 days, but graft survival >30 days has been unusual until recently. METHODS: Donor pigs (n=4) were on an α1,3-galactosyltransferase gene-knockout (GTKO)/human complement regulatory protein (CD46) background (GTKO/CD46). In addition, the pigs were transgenic for at least one human coagulation regulatory protein...
March 17, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28297082/blood-product-utilization-in-human-upper-extremity-transplantation-challenges-complications-considerations-and-transfusion-protocol-conception
#16
Jay S Raval, Vijay S Gorantla, Jaimie T Shores, W P Andrew Lee, Raymond M Planinsic, Marian A Rollins-Raval, Gerald Brandacher, Karen E King, Joseph E Losee, Joseph E Kiss
BACKGROUND: Upper-extremity transplantation (UET) is a reality. Immunologic, functional, and graft survival outcomes have been encouraging. However, these complex reconstructions have unique considerations that pose distinct challenges. Transplant programs have reported morbidity and mortality due to significant intraoperative blood losses, but similar data are scant during other phases of recovery. We report experience from two centers on complete blood component demands and utilization with UET...
March 2017: Transfusion
https://www.readbyqxmd.com/read/28296255/breg-dependent-islet-transplant-tolerance-is-also-nk-cell-dependent
#17
Christian Schuetz, Kang Mi Lee, Ryan Scott, Lisa Kojima, Laura Washburn, Liye Liu, Wei-Hui Liu, Haley Tector, Ji Lei, Heidi Yeh, James Kim, James F Markmann
Immunologic tolerance to solid organ and islet cell grafts has been achieved in various rodent models using antibodies directed at CD45RB and Tim-1. We have shown that this form of tolerance depends on regulatory B-cells. To elucidate further the mechanism by which Bregs induce tolerance we investigated the requirement of NK and NKT cells in this model. To do so, hyperglycemic B6, μMT, Beige or CD1d(-/-) mice received Balb/c islet grafts and treatment with the tolerance inducing regimen consisting of anti-CD45RB and anti -TIM1...
March 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28296035/sepsis-after-renal-transplantation-clinical-immunological-and-microbiological-risk-factors
#18
Thomas Schachtner, Maik Stein, Petra Reinke
BACKGROUND: As immunosuppressive therapy and allograft survival have improved, the increased incidence of sepsis has become a major hurdle of disease-free survival after renal transplantation. METHODS: We identified 112 of 957 kidney transplant recipients (KTRs) with sepsis. 31 KTRs developed severe sepsis or septic shock, and 30 KTRs died from sepsis. KTRs without sepsis were used for comparison. CMV-specific and alloreactive T-cells were measured using an interferon-γ Elispot-assay...
March 11, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28295181/long-term-follow-up-of-patients-receiving-allogeneic-stem-cell-transplant-for-chronic-lymphocytic-leukaemia-mixed-t-cell-chimerism-is-associated-with-high-relapse-risk-and-inferior-survival
#19
Philip A Thompson, Francesco Stingo, Michael J Keating, William G Wierda, Susan M O'Brien, Zeev Estrov, Celina Ledesma, Katayoun Rezvani, Muzaffar Qazilbash, Nina Shah, Simrit Parmar, Uday Popat, Paolo Anderlini, Nieto Yago, Stefan O Ciurea, Partow Kebriaei, Richard Champlin, Elizabeth J Shpall, Chitra M Hosing
There is limited information regarding the immunological predictors of post-allogeneic stem cell transplant (alloSCT) outcome in chronic lymphocytic leukaemia (CLL), such as mixed T-cell chimerism. We analysed 143 consecutive patients with relapsed/refractory CLL, transplanted between 2000 and 2012, to determine the prognostic relevance of mixed chimerism post-alloSCT and the ability of post-transplant immunomodulation to treat relapse. Mixed T-cell chimerism occurred in 50% of patients at 3 months and 43% at 6 months post-alloSCT; upon 3- and 6-month landmark analysis, this was associated with inferior progression-free survival (PFS) [Hazard ratio (HR) 1·93, P = 0·003 and HR 2·58, P < 0·001] and survival (HR 1·66, P = 0·05 and HR 2·17, P < 0·001), independent of baseline patient characteristics, and a lower rate of grade II-IV acute graft-versus-host disease (GHVD) (16% vs...
March 14, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28289675/humoral-immunodeficiency-with-hypotonia-feeding-difficulties-enteropathy-and-mild-eczema-caused-by-a-classical-foxp3-mutation
#20
Paul Tuijnenburg, Eloy Cuadrado, Annet M Bosch, Angelika Kindermann, Machiel H Jansen, Marielle Alders, Ester M M van Leeuwen, Taco W Kuijpers
We describe here the case of a boy who presented with pulmonary infections, feeding difficulties due to velopharyngeal insufficiency and gastroesophageal reflux, myopathy, and hypotonia soon after birth. Later, he was also found to have an elevated immunoglobulin (Ig) E and mild eczema and was diagnosed with inflammatory bowel disease. Further immunological screening at the age of 7 years showed low B and NK cell numbers but normal CD4(+) and CD8(+) T cells and notably, normal numbers of CD4(+) regulatory T (Treg) cells...
2017: Frontiers in Pediatrics
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